Immunostimulatory activity of the aqueous extract from the leaves of Sambucus racemosa subsp. pendula through TLR4­dependent JNK activation in RAW264.7 cells.

Sambucus racemosa subsp. pendula (SRP) is an endemic plant of Korea, exclusively found on Ulleungdo Island. SRP is widely used as both a traditional medicine and food source. However, there is a lack of research on the pharmacological activities of SRP. Therefore, the present study aimed to explore the potential use of SRP leaves (SRPL) as a natural immunostimulant by analyzing its macrophage activation properties and the underlying mechanisms of action. Among the various extraction conditions, SRPL (AE20-SRPL) extracted with 100% distilled water at 20˚C induced the highest nitric oxide (NO) production in RAW264.7 cells. Thus, the further studies were performed using AE20-SRPL. AE20-SRPL increased the production of immunostimulatory factors such as NO, prostaglandin E2, inducible nitric oxide synthase, cyclooxygenase-2, IL-1ß and TNF-α and phagocytosis in a dose-dependent manner in RAW264.7 cells without exhibiting cytotoxicity. Among Toll-like receptor (TLR)2 and TLR4, inhibition of TLR4 significantly reduced AE20-SRPL-mediated increases in the production of immunostimulatory factors and phagocytosis in RAW264.7 cells. Furthermore, in RAW264.7 cells, inhibition of JNK, one of the components of MAPK signaling along with ERK1/2 and p38, attenuated the AE20-SRPL-mediated increases in the production of immunostimulatory factors and phagocytosis. Additionally, AE20-SRPL induced the phosphorylation of JNK and inhibition of TLR4 reduced AE20-SRPL-mediated JNK phosphorylation. These results suggested that AE20-SRPL may enhance the production of immunostimulatory factors and phagocytosis through TLR4-dependent activation of JNK in macrophages. Although the present study is limited to in vitro research using a cell model, AE20-SRPL demonstrated potential as a natural material capable of inducing macrophage activation for immune enhancement.

Contrast enhancement patterns associated with acute stroke in moyamoya disease using MR vessel wall imaging.

BACKGROUND AND PURPOSE: High-resolution magnetic resonance imaging (HR-MRI) can provide valuable insights into the histopathological characteristics of moyamoya disease (MMD). However, the patterns of vessel wall contrast enhancement have not been well established. We aimed to identify the contrast enhancement patterns of the vessel walls associated with acute cerebral infarction using HR-MRI in MMD. METHODS: In this retrospective study, we conducted genetic tests for Ring Finger Protein 213 (RNF 213) and performed HR-MRI on patients suspected of having MMD. We analyzed wall enhancement patterns including concentric, eccentric, or mixed enhancement types, and the occurrence of acute cerebral infarction in patients who simultaneously tested positive for RNF 213 and exhibited definite features of MMD on HR-MRI. RESULTS: Among 306 patients who underwent RNF 213 tests for the evaluation of MMD, 56 showed positive RNF 213, and HR-MRI was performed on 32 of them. Among the patients with acute cerebral infarction, the incidence rate was significantly higher in the group with concentric wall enhancement compared to patients without acute cerebral infarction (73.3% vs. 17.0%, p < .002). Furthermore, the incidence was notably elevated, even in patients with pure concentric wall enhancement (40.0% vs. 5.9%, p = .033). The area under the curve (AUC) for the group with any concentric wall enhancement showed a significant result of .78 (95% confidence interval [CI]: .61-.95, p = .007), whereas the predictive ability for pure concentric wall enhancement did not reach significance (AUC = .67, 95% CI: .48-.86, p = .100). CONCLUSIONS: Concentric wall enhancement was a significant predictor of acute cerebral infarction in patients with MMD.

Outcomes in patients with out-of-hospital cardiac arrest according to prehospital advanced airway management timing: a retrospective observational study.

Background: In patients with out-of-hospital cardiac arrest (OHCA), guidelines recommend advanced airway (AA) management at the advanced cardiovascular life support stage; however, the ideal timing remains controversial. Therefore, we evaluated the prognosis according to the timing of AA in patients with OHCA. Methods: We conducted a retrospective observational study of patients with OHCA at six major hospitals in Daegu Metropolitan City, South Korea, from August 2019 to June 2022. We compared groups with early and late AA and evaluated prognosis, including recovery of spontaneous circulation (ROSC), survival to discharge, and neurological evaluation, according to AA timing. Results: Of 2,087 patients with OHCA, 945 underwent early AA management and 1,142 underwent late AA management. The timing of AA management did not influence ROSC in the emergency department (5-6 minutes: adjusted odds ratio [aOR], 0.97; p=0.914; 7-9 minutes: aOR, 1.37; p=0.223; ≥10 minutes: aOR, 1.32; p=0.345). The timing of AA management also did not influence survival to discharge (5-6 minutes: aOR, 0.79; p=0.680; 7-9 minutes: aOR, 1.04; p=0.944; ≥10 minutes: aOR, 1.86; p=0.320) or good neurological outcomes (5-6 minutes: aOR, 1.72; p=0.512; 7-9 minutes: aOR, 0.48; p=0.471; ≥10 minutes: aOR, 0.96; p=0.892). Conclusion: AA timing in patients with OHCA was not associated with ROSC, survival to hospital discharge, or neurological outcomes.

Radiographic and Clinical Outcomes of Transverse Process Hook Placement at the Proximal Thoracic Upper Instrumented Vertebra in Adult Spinal Deformity Surgery.

OBJECTIVE: Few studies have reported radiographic and clinical outcomes of transverse process hook (TPH) placement at the proximal thoracic upper instrumented vertebra (UIV) in adult spinal deformity (ASD) surgery. This study aims to investigate radiographic and clinical outcomes of TPH placement at the UIV for ASD surgery. METHODS: This is a retrospective cohort of 56 patients with ASD (age, 59 ± 13 years; followup, 44 ± 19 months) from Johns Hopkins Hospital, who underwent long posterior spinal fusion to the proximal thoracic spine (T2-5). Visual analogue scale (VAS) for back pain, Oswestry Disability Index (ODI), 36-item Short Form health survey scores, thoracic kyphosis (TK), lumbar lordosis, sacral slope, pelvic tilt, pelvic incidence, proximal junctional kyphosis (PJK) angle, PJK incidence, pattern of PJK, grades of TPH dislodgement, revision surgery, and factors associated with high-grade TPH dislodgement were analyzed. RESULTS: VAS for back pain and ODI values improved significantly from preoperatively to final follow-up. Mean change in PJK angle was 12° (range, 0.5°-43°). Twenty patients (36%) developed PJK, of whom 13 had compression fractures at 1 vertebra distal to the UIV (UIV-1). Final TPH position was stable in 42 patients (75%). In most patients (86%), TPH dislodgement did not progress after 6-month postoperative follow-up. Three patients (5.3%) underwent revision surgery to extend the fusion because of symptomatic PJK. Unstable TPH position was associated only with revision surgery and TK. CONCLUSION: TPH placement at the proximal thoracic UIV for long fusion showed favorable clinical and radiographic outcomes in terms of the incidence of PJK and mean PJK angle at mean 44-month follow-up. TPHs placed in the proximal thoracic UIV were in stable position in 75% of patients. Compression fracture at UIV-1 was the most common pattern of PJK. PJK angle progression was greater in revision cases and in patients with greater preoperative thoracic kyphosis.

Mode of Action of Antimicrobial Potential Protease SH21 Derived from Bacillus siamensis.

Global public health is facing a major issue with emerging resistance to antimicrobial agents. Antimicrobial agents that are currently on the market are strong and efficient, but it has not been ruled out that these medications will eventually cause resistance to bacteria. Exploring novel bioactive compounds derived from natural sources is therefore, crucial to meet future demands. The present study evaluated the mode of action of the antimicrobial potential protease enzyme SH21. Protease SH21 exhibited antimicrobial activity, strong heat stability (up to 100 °C), and pH stability (pH 3.0 to 9.0). In terms of mode of action, we found that protease SH21 was able to disrupt the bacterial cell membrane as the results of the nucleotide leakage and cell membrane permeability assay. In addition, we also checked inner membrane permeability by PI uptake assay which suggested that protease SH21 has the ability to enter the bacterial cell membrane. Our results revealed that the antimicrobial protease SH21 might be a promising candidate for treating microbial infections.

Variations in Risk Factors across Different Periods of Stroke and Transient Ischemic Attack Recurrence.

INTRODUCTION: Accurately discerning periods of heightened risk of stroke or transient ischemic attack (TIA) recurrence and managing modifiable risk factors are essential for minimizing overall recurrence risk. This study identified differences in the timing of stroke or TIA recurrence based on risk factors and patient characteristics to develop strategies for reducing recurrence in clinical practice. METHODS: We retrospectively selected patients with ischemic stroke or TIA at the Korea University Ansan Hospital Stroke Center between March 2014 and December 2021 using the prospective institutional database of the Korea University Stroke Registry. We collected demographic, clinical data and categorized participants by recurrence timing (early within or late after 3 months). Using multinomial logistic regression analysis, we examined variables associated with early and late recurrent stroke or TIAs. RESULTS: Among 3,646 patients, 255 experienced a recurrent stroke or TIA and 3,391 experienced their first stroke or TIA. Multinomial logistic regression analysis revealed significant associations between early recurrent stroke or TIA and diabetes mellitus (odds ratio [OR] 1.98, 95% confidence interval [CI] 1.25-3.15), other determined etiologies in the Trial of Org 10172 in the Acute Stroke Treatment classification (OR 3.00, 95% CI 1.37-6.61), and white matter changes (OR 1.97, 95% CI 1.17-3.33). Late recurrence showed a significant correlation with TIA (OR 2.95, 95% CI 1.52-5.71) and cerebral microbleeds (OR 2.22, 95% CI 1.32-3.75). CONCLUSION: Substantial differences in factors contribute to stroke or TIA recurrence based on timing. Managing the risk of recurrence in clinical practice necessitates accurate identification of heightened risk periods and rigorous control of modifiable risk factors.

Localization of solar panel cleaning robot combining vision processing and extended Kalman filter.

In this study, we introduce a method for estimating the position of a self-driving solar panel-cleaning mobile robot. This estimation relies on line counts, typically 16 cm in panel width, obtained through image processing on the panel floor, along with wheel encoder information and inertial sensor data. To achieve accurate line counts, we introduce two adjusted threshold values and allow offsets in these values based on the robot's speed. Additionally, inertial measurement unit (IMU) signals assist in determining whether a line is horizontal or vertical, depending on the robot's movement direction on the panel, utilizing the robot's heading angle and detected line angle. When the robot is positioned between lines on the panel, more precise location estimation is necessary beyond simple line counts. To tackle this challenge, we integrate the extended Kalman filter with IMU data and encoder information, significantly enhancing position estimation. This integration achieves an RMSE accuracy value of up to 0.089 m, notably at a relatively high speed of 100 mm/s. This margin of error is almost half that of the vision-based line-counting method.

Distal normal vessel diameter might be associated with silent brain infarcts after stenting for symptomatic carotid stenosis.

BACKGROUND: Carotid artery stenting (CAS) has been the standard treatment for carotid stenosis because it is less invasive; however, the risk of periprocedural thromboembolism is high. We investigated the predictors for silent brain infarcts (SBIs), focusing on embolic protection in CAS. METHODS: This study was single-center retrospective study, and we obtained baseline demographics and clinical, laboratory, and periprocedural variables of patients who underwent CAS. Also, methods used for embolic protection (no EPD, distal EPD, or proximal balloon guiding catheter) during CAS were obtained. Distal normal vessel diameter was defined as the diameter of cervical internal carotid artery where the artery wall becomes parallel. Diffusion-weighted imaging was performed before and after procedure to detect SBIs. The primary outcome was stented territory SBIs, and the secondary outcomes were any territories SBIs and stented territory SBIs in cases with EPD. RESULTS: A total of 196 CAS procedures with mean age 69.1 ± 9.9 years were included. After CAS, stented territory SBIs occurred in 53 (27.0 %) cases and any territories SBIs in 60 (30.6 %) cases. Univariable analyses revealed that distal normal vessel diameter (odds ratio = 1.71, 95 % confidence interval = 1.20-2.43, P = 0.003) was associated with the occurrence of stented territory SBIs after CAS. After adjusting for potential variables, larger distal normal vessel diameter (1.61 [1.10-2.36], P = 0.014) increased the occurrence of SBIs after CAS. Consistent results were obtained when the outcome was any territories SBIs or stented territory SBIs in cases with EPD. CONCLUSIONS: Distal normal vessel diameter was a predictor for the occurrence of SBI after CAS. The passable pore size of EPDs may vary depending on vessel diameter, and may impact the occurrence of SBIs.

Cytosine Deaminase-Overexpressing hTERT-Immortalized Human Adipose Stem Cells Enhance the Inhibitory Effects of Fluorocytosine on Tumor Growth in Castration Resistant Prostate Cancer.

A promising de novo approach for the treatment of Castration-resistant prostate cancer (CRPC) exploits cell-mediated enzyme prodrug therapy comprising cytosine deaminase (CD) and fluorouracil (5-FC). The aim of this study was to determine the potential of bacterial CD-overexpressing hTERT-immortalized human adipose stem cells (hTERT-ADSC.CD) to suppress CRPC. A lentiviral vector encoding a bacterial CD gene was used to transfect and to generate the hTERT-ADSC.CD line. The ability of the cells to migrate selectively towards malignant cells was investigated in vitro. PC3 and hTERT-ADSC.CD cells were co-cultured. hTERT-ADSC.CD and 1 × 106 PC3 cells were administered to nude mice via intracardiac and subcutaneous injections, respectively, and 5-FC was given for 14 days. hTERT-ADSC.CD were successfully engineered. Enhanced in vitro hTERT-ADSC.CD cytotoxicity and suicide effect were evident following administration of 5 µM 5-FC. hTERT-ADSC.CD, together with 5-FC, augmented the numbers of PC3 cells undergoing apoptosis. In comparison to controls administered hTERT-ADSC.CD monotherapy, hTERT-ADSC.CD in combination with 5-FC demonstrated a greater suppressive effect on tumor. In CPRC-bearing mice, tumor suppression was enhanced by the combination of CD-overexpressing ADSC and the prodrug 5-FC. Stem cells exhibiting CD gene expression are a potential novel approach to treatment for CRPC.

Cervical sagittal parameters in degenerative cervical spondylolisthesis versus degenerative cervical kyphosis with myeloradiculopathy treated by anterior cervical discectomy and fusion.

Background: Adult spinal deformity, especially sagittal imbalance, is affecting health-related quality-of-life (HRQOL) scores. There is a lack of emphasis in the comparison of cervical sagittal parameters in patients with degenerative cervical spondylolisthesis and degenerative cervical kyphosis. The aim of study is to determine the preoperative and postoperative cervical sagittal parameters in myeloradiculopathic patients with degenerative cervical spondylolisthesis and degenerative cervical kyphosis treated by anterior cervical discectomy and fusion (ACDF). Methods: A retrospective medical records and radiographic study of 30 adult patients were reviewed. Fifteen patients with degenerative cervical spondylolisthesis and 15 patients with degenerative cervical kyphosis have been performed ACDF from 2010-2020. We measured the preoperative and postoperative cervical sagittal parameters: C0-C2 angle, C1-C2 angle, C2-C7 angle, C2-C7 sagittal vertical axis (SVA), T1 slope, neck tilt angle and thoracic inlet angle. Minimum follow-up period was at least 2 years. Results: Patients in degenerative cervical kyphosis group have C2-C7 angle less than degenerative cervical spondylolisthesis group (-14.88±7.32 vs. 9.60±13.60), leading to increase the mismatch between T1 slope and C2-C7 angle in kyphotic group and hyperlordosis of C0-C2 angle and C1-C2 angle (31.13±7.68, 37.88±5.08) compare with spondylolisthesis group (13±10.20, 24.60±10.70). Whereas patients with degenerative cervical spondylolisthesis have C2-C7 SVA (33.22±13.92) more than kyphosis group (13.70±13.60). After surgery, there is significant increase of the C2-C7 angle in the kyphosis group compare before and after surgery (-14.88±7.32 vs. 4.10±11.80). While the spondylolisthesis group has no significantly different parameters compare to before surgery. However, the postoperative cervical sagittal parameters of all patients are within the normal thresholds (T1-Slope minus C2-C7 lordosis <15° and C2-C7 SVA <40 mm). Conclusions: The study demonstrates the difference of sagittal parameters between degenerative cervical spondylolisthesis and kyphosis before and after surgery. ACDF not only provides neural decompressive procedure, but also corrects the regional cervical sagittal parameters.

Interleukin-1α links peripheral CaV2.2 channel activation to rapid adaptive increases in heat sensitivity in skin.

Neurons have the unique capacity to adapt output in response to changes in their environment. Within seconds, sensory nerve endings can become hypersensitive to stimuli in response to potentially damaging events. The underlying behavioral response is well studied, but several of the key signaling molecules that mediate sensory hypersensitivity remain unknown. We previously discovered that peripheral voltage-gated CaV2.2 channels in nerve endings in skin are essential for the rapid, transient increase in sensitivity to heat, but not to mechanical stimuli, that accompanies intradermal capsaicin. Here we report that the cytokine interleukin-1α (IL-1α), an alarmin, is necessary and sufficient to trigger rapid heat and mechanical hypersensitivity in skin. Of 20 cytokines screened, only IL-1α was consistently detected in hind paw interstitial fluid in response to intradermal capsaicin and, similar to behavioral sensitivity to heat, IL-1α levels were also dependent on peripheral CaV2.2 channel activity. Neutralizing IL-1α in skin significantly reduced capsaicin-induced changes in hind paw sensitivity to radiant heat and mechanical stimulation. Intradermal IL-1α enhances behavioral responses to stimuli and, in culture, IL-1α enhances the responsiveness of Trpv1-expressing sensory neurons. Together, our data suggest that IL-1α is the key cytokine that underlies rapid and reversible neuroinflammatory responses in skin.

Ultrathin All-Solid-State MoS2-Based Electrolyte Gated Synaptic Transistor with Tunable Organic-Inorganic Hybrid Film.

Electrolyte-gated synaptic transistors (EGSTs) have attracted considerable attention as synaptic devices owing to their adjustable conductance, low power consumption, and multi-state storage capabilities. To demonstrate high-density EGST arrays, 2D materials are recommended owing to their excellent electrical properties and ultrathin profile. However, widespread implementation of 2D-based EGSTs has challenges in achieving large-area channel growth and finding compatible nanoscale solid electrolytes. This study demonstrates large-scale process-compatible, all-solid-state EGSTs utilizing molybdenum disulfide (MoS2) channels grown through chemical vapor deposition (CVD) and sub-30 nm organic-inorganic hybrid electrolyte polymers synthesized via initiated chemical vapor deposition (iCVD). The iCVD technique enables precise modulation of the hydroxyl group density in the hybrid matrix, allowing the modulation of proton conduction, resulting in adjustable synaptic performance. By leveraging the tunable iCVD-based hybrid electrolyte, the fabricated EGSTs achieve remarkable attributes: a wide on/off ratio of 109, state retention exceeding 103, and linear conductance updates. Additionally, the device exhibits endurance surpassing 5 × 104 cycles, while maintaining a low energy consumption of 200 fJ/spike. To evaluate the practicality of these EGSTs, a subset of devices is employed in system-level simulations of MNIST handwritten digit recognition, yielding a recognition rate of 93.2%.

Interleukin-1α links peripheral CaV2.2 channel activation to rapid adaptive increases in heat sensitivity in skin.

Neurons have the unique capacity to adapt output in response to changes in their environment. Within seconds, sensory nerve endings can become hypersensitive to stimuli in response to potentially damaging events. The underlying behavioral response is well studied, but several of the key signaling molecules that mediate sensory hypersensitivity remain unknown. We previously discovered that peripheral voltage-gated CaV2.2 channels in nerve endings in skin are essential for the rapid, transient increase in sensitivity to heat, but not to mechanical stimuli, that accompanies intradermal capsaicin. Here we report that the cytokine interleukin-1α (IL-1α), an alarmin, is necessary and sufficient to trigger rapid heat and mechanical hypersensitivity in skin. Of 20 cytokines screened, only IL-1α was consistently detected in hind paw interstitial fluid in response to intradermal capsaicin and, similar to behavioral sensitivity to heat, IL-1α levels were also dependent on peripheral CaV2.2 channel activity. Neutralizing IL-1α in skin significantly reduced capsaicin-induced changes in hind paw sensitivity to radiant heat and mechanical stimulation. Intradermal IL-1α enhances behavioral responses to stimuli and, in culture, IL-1α enhances the responsiveness of Trpv1-expressing sensory neurons. Together, our data suggest that IL-1α is the key cytokine that underlies rapid and reversible neuroinflammatory responses in skin.

Activation of hypoactive parvalbumin-positive fast-spiking interneuron restores dentate inhibition to prevent epileptiform activity in the mouse intrahippocampal kainate model of temporal lobe epilepsy.

Parvalbumin-positive (PV+) GABAergic interneurons in the dentate gyrus provide powerful perisomatic inhibition of dentate granule cells (DGCs) to prevent overexcitation and maintain the stability of dentate gyrus circuits. Most dentate PV+ interneurons survive status epilepticus, but surviving PV+ interneuron mediated inhibition is compromised in the dentate gyrus shortly after status epilepticus, contributing to epileptogenesis in temporal lobe epilepsy. It is uncertain whether the impaired activity of dentate PV+ interneurons recovers at later times or if it continues for months following status epilepticus. The development of compensatory modifications related to PV+ interneuron circuits in the months following status epilepticus is unknown, although reduced dentate GABAergic inhibition persists long after status epilepticus. We employed PV immunostaining and whole-cell patch-clamp recordings from dentate PV+ interneurons and DGCs in slices from male and female sham controls and intrahippocampal kainate (IHK) treated mice that developed spontaneous seizures months after status epilepticus to study epilepsy-associated changes in dentate PV+ interneuron circuits. We found that the number of dentate PV+ cells was reduced in IHK treated mice. Electrical recordings showed that: 1) Action potential firing rates of dentate PV+ interneurons were reduced in IHK treated mice up to four months after status epilepticus; 2) Spontaneous inhibitory postsynaptic currents (sIPSCs) in DGCs exhibited reduced frequency but increased amplitude in IHK treated mice; and 3) The amplitude of evoked IPSCs in DGCs by optogenetic activation of dentate PV+ cells was upregulated without changes in short-term plasticity. Video-EEG recordings revealed that IHK treated mice showed spontaneous epileptiform activity in the dentate gyrus and that chemogenetic activation of PV+ interneurons abolished the epileptiform activity. Our results suggest not only that the compensatory changes in PV+ interneuron circuits develop after IHK treatment, but also that increased PV+ interneuron mediated inhibition in the dentate gyrus may compensate for cell loss and reduced intrinsic excitability of dentate PV+ interneurons to stop seizures in temporal lobe epilepsy. Highlights: Reduced number of dentate PV+ interneurons in TLE micePersistently reduced action potential firing rates of dentate PV+ interneurons in TLE miceEnhanced amplitude but decreased frequency of spontaneous IPSCs in the dentate gyrus in TLE miceIncreased amplitude of evoked IPSCs mediated by dentate PV+ interneurons in TLE miceChemogenetic activation of PV+ interneurons prevents epileptiform activity in TLE mice.

Preparation of human astrocytes with potent therapeutic functions from human pluripotent stem cells using ventral midbrain patterning.

INTRODUCTION: Astrocytes are glial-type cells that protect neurons from toxic insults and support neuronal functions and metabolism in a healthy brain. Leveraging these physiological functions, transplantation of astrocytes or their derivatives has emerged as a potential therapeutic approach for neurodegenerative disorders. METHODS: To substantiate the clinical application of astrocyte-based therapy, we aimed to prepare human astrocytes with potent therapeutic capacities from human pluripotent stem cells (hPSCs). To that end, we used ventral midbrain patterning during the differentiation of hPSCs into astrocytes, based on the roles of midbrain-specific factors in potentiating glial neurotrophic/anti-inflammatory activity. To assess the therapeutic effects of human midbrain-type astrocytes, we transplanted them into mouse models of Parkinson's disease (PD) and Alzheimer's disease (AD). RESULTS: Through a comprehensive series of in-vitro and in-vivo experiments, we were able to establish that the midbrain-type astrocytes exhibited the abilities to effectively combat oxidative stress, counter excitotoxic glutamate, and manage pathological protein aggregates. Our strategy for preparing midbrain-type astrocytes yielded promising results, demonstrating the strong therapeutic potential of these cells in various neurotoxic contexts. Particularly noteworthy is their efficacy in PD and AD-specific proteopathic conditions, in which the midbrain-type astrocytes outperformed forebrain-type astrocytes derived by the same organoid-based method. CONCLUSION: The enhanced functions of the midbrain-type astrocytes extended to their ability to release signaling molecules that inhibited neuronal deterioration and senescence while steering microglial cells away from a pro-inflammatory state. This success was evident in both in-vitro studies using human cells and in-vivo experiments conducted in mouse models of PD and AD. In the end, our human midbrain-type astrocytes demonstrated remarkable effectiveness in alleviating neurodegeneration, neuroinflammation, and the pathologies associated with the accumulation of α-synuclein and Amyloid ß proteins.

High-frequency ultrasound-assisted perforator mapping enhances efficiency in microsurgical reconstruction using thin ALT and SCIP flaps.

BACKGROUND: With the growing demand for the use of thin perforator flaps, obtaining knowledge on the superficial anatomy of perforators is imperative for stable flap elevation. Conventional modalities for perforator mapping fall short in providing such information. High-frequency ultrasound (HFUS), known for visualizing the superficially located anatomic structures, may potentially fill this void. This study aimed to evaluate the effectiveness of HFUS in the outcome of anterolateral thigh (ALT) and superficial circumflex iliac artery perforator (SCIP) flap-based reconstructions. METHODS: Consecutive patients who underwent free ALT or SCIP flap-based reconstruction from January 2021 to November 2022 were retrospectively reviewed. Perforator mapping was conducted using a handheld Doppler during the first year, while HFUS was used in the latter part. The two techniques were compared in terms of flap harvesting time and perfusion-related complication rates while considering the flap elevation plane. RESULTS: In total, 123 cases were analyzed, including 82 ALT flaps (41 in each group) and 41 SCIP flaps (16 in the Doppler and 25 in the HFUS group). The time required for flap elevation exhibited a tendency to decrease in the HFUS group, with a significant difference observed in cases involving thin flap elevation (super-thin ALT flaps and pure-skin-perforator SCIP flaps). Compared with the Doppler group, the HFUS group demonstrated significantly lower rates of PRCs, particularly partial flap necrosis. This difference remained significant in multivariable analyses. CONCLUSION: Our results suggest that HFUS might be an appealing modality for perforator mapping in cases requiring thin ALT and SCIP flap.

Safety and efficacy of pelvic arterial embolization for primary postpartum hemorrhage in hemodynamically stable and hemodynamically unstable patients: Is it "time" for a paradigm change?

BACKGROUND: Pelvic artery embolization (PAE) is an effective and safe technique for treating postpartum hemorrhage (PPH) with hemodynamic stability. However, its use in hemodynamically unstable patients remains controversial. PURPOSE: To determine the safety and efficacy of pelvic arterial embolization (PAE) according to the hemodynamic state of primary postpartum hemorrhage (PPH) patients. METHODS: This cohort study was conducted retrospectively, using data from January 2004 to December 2021, in a resource-rich setting at a tertiary Level 1 trauma academic center. A total of 437 patients were diagnosed with PPH during the study period. Of these 437 patients, 161 with primary PPH who underwent PAE were enrolled in the study. The outcomes assessed included the clinical success rate, mortality, the overall success rate, predictive factors for failed PAE, and time-dependent changes in hemodynamic parameters, such as systolic blood pressure (SBP), heart rate (HR), and shock index (SI). Propensity score (PS) matching analysis was performed to assess the influence of specific variables or conditions on the outcomes. RESULTS: Of the 161 patients who underwent PAE for primary PPH (mean age, 32.9 ± 4.3 [SD]), 85 were retrospectively categorized as having hemodynamic stability (mean age, 32.6 ± 4.1 [SD]), while 76 were categorized as having hemodynamic instability (mean age, 33.3 ± 4.4 [SD]). This study showed PAE for primary PPH had a success rate of 91.9 %, with no significant difference in mortality rates between the groups. The clinical success rate was 98.8 % for patients with hemodynamic stability and 84.2 % for those with hemodynamic instability (p < .001). The overall success rate was 98.8 % for hemodynamic stability and 89.5 % for hemodynamic instability (p = .014). After propensity score matching, the clinical success rate was higher in hemodynamically stable patients than in unstable ones (100 % vs. 86.3 %, p = .013). However, there was no significant difference in the overall success rate (100 % vs. 90.2 %, p = .056). Among the PS-matched population, predictive factors for the failed PAE in primary PPH were hemodynamic instability (adjusted odds ratio [aOR] 21.22, 95 % CI 1.27-355.76; p = .034) and emergency Cesarean delivery with accompanying hemorrhag (aOR 54.00, 95 % CI 11.93-244.56; p = .008). In three groups within a PS-matched population - hemodynamically stable, unstable with successful outcomes, and unstable with unsuccessful outcomes, a generalized linear mixed model (GLMM) analysis for time-dependent changes in hemodynamic parameters revealed a statistically significant difference in SBP, HR, and SI at various time points. CONCLUSION: Pelvic arterial embolization of primary postpartum bleeding in hemodynamic instability has been identified as an alternative, safe, and effective life-saving procedure for multidisciplinary treatment in resource-rich environments even after the baseline characteristics are balanced by the PS matching, suggesting it is a primary care option.

Association of cranial base suture/synchondrosis fusion with severity of increased intracranial pressure in Crouzon syndrome.

This study investigated how the fusion states of the cranial base is related to the degree of increased intracranial pressure (ICP) in patients with Crouzon syndrome. This retrospective cohort study enrolled patients who were diagnosed with Crouzon syndrome between May 2007 and April 2022. We categorized the patients into three groups: A, B, and C, according to the severity of increased ICP and the number of cranial vault remodeling procedures for corrective operation. The preoperative fusion states of the cranial base sutures/synchondroses were examined using facial bone computed tomography and compared between groups. Overall, 22 patients were included in Groups A, B, and C, including 8, 7, and 7 patients, respectively. The preoperative average grades of the total cranial base suture/synchondrosis fusion appeared to significantly increase with severity, except for the frontoethmoidal suture, which showed the opposite tendency. In the subgroup analysis, frontosphenoidal, sphenoparietal, sphenosquamosal, parietomastoid, and occipitomastoid suture and petro-occipital synchondrosis were associated with earlier fusion in the more severe group. Premature closure of the cranial base sutures/synchodroses seems to be associated with increased ICP severity in patients with Crouzon syndrome. Precise evaluation of minor sutures/synchondroses at the first visit might help build subsequent operative plans and predict disease prognosis.

Bounded contribution of human early visual cortex to the topographic anisotropy in spatial extent perception.

To interact successfully with objects, it is crucial to accurately perceive their spatial extent, an enclosed region they occupy in space. Although the topographic representation of space in the early visual cortex (EVC) has been favored as a neural correlate of spatial extent perception, its exact nature and contribution to perception remain unclear. Here, we inspect the topographic representations of human individuals' EVC and perception in terms of how much their anisotropy is influenced by the orientation (co-axiality) and radial position (radiality) of stimuli. We report that while the anisotropy is influenced by both factors, its direction is primarily determined by radiality in EVC but by co-axiality in perception. Despite this mismatch, the individual differences in both radial and co-axial anisotropy are substantially shared between EVC and perception. Our findings suggest that spatial extent perception builds on EVC's spatial representation but requires an additional mechanism to transform its topographic bias.